Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• The serological diversity of serum IgG/IgA/IgM against the SARS-CoV-2 nucleoprotein, spike, and receptor-binding domain and neutralizing antibodies in patients with COVID-19 in Japan -

  Objectives: To compare the temporal changes of IgM, IgG, and IgA antibodies against the SARS-CoV-2 nucleoprotein, S1 subunit, and receptor binding domain and neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with COVID-19. Methods: A total of five patients in Nissan Tamagawa Hospital, Tokyo, Japan confirmed COVID-19 from August 8, 2020 to August 14, 2020 were investigated. Serum samples were acquired multiple times from 0 to 76 days after symptom onset. Using a fully automated CLIA analyzer, we measured the levels of IgG, IgA, and IgM against the SARS-CoV-2 N, S1, and RBD and NAbs against SARS-CoV-2. Results: The levels of IgG antibodies against SARS-CoV-2 structural proteins increased over time in all cases but IgM and IgA levels against SARS-CoV-2 showed different increasing trends among individuals in the early stage. In particular, we observed IgA antibodies increasing before IgG and IgM in 3/5 cases. The NAb levels against SARS-CoV-2 increased and kept above 10 AU/mL more than around 70 days after symptom onset in all cases. Furthermore, in the early stage, NAb levels were more than cut off value in 4/5 COVID-19 patients some of whose antibodies against RBD didn9t exceed 10 AU/mL. Conclusions: Our findings indicate that patients with COVID-19 should be examined for IgG, IgA and IgM antibodies against SARS-CoV-2 structural proteins and NAbs against SARS-CoV-2 in addition to conventional antibody testing methods for SARS-CoV-2 (IgG and IgM kits) to analyze the diversity of patients9 immune mechanisms.

  🖺 Full Text HTML: The serological diversity of serum IgG/IgA/IgM against the SARS-CoV-2 nucleoprotein, spike, and receptor-binding domain and neutralizing antibodies in patients with COVID-19 in Japan
• Hidden fraction of Polish population immune to SARS-CoV-2 in May 2021 -

  Population immunity to SARS-CoV-2 derives from two well-defined and controlled sources: vaccinations or diagnosed and registered cases of the disease. It may however also result from asymptomatic, oligosymptomatic, or even full-blown but undiagnosed and unregistered cases from which patients recovered at home. Here we present a population screening for SARS-CoV-2 specific IgG and IgA antibodies in Polish citizens (healthy adults, N=501) who had never been positively diagnosed with or vaccinated against SARS-CoV-2. Blood samples were collected in Wrocław (Lower Silesia) on 15th and 22nd May 2021. Sera from COVID-19 patients with a severe course (hospitalized) (N=43) or had been vaccinated (N=14) served as a positive control. The patients were tested with Microblot-Array COVID-19 IgG and IgA (quantitative) that contain specific SARS-CoV-2 antigens: NCP, RBD, Spike S2, E, ACE2, PLPro protein, as well as antigens for exclusion cross-reactivity with other coronaviruses: MERS-CoV, SARS-CoV, HCoV 229E Np, HCoV NL63 Np. Within the investigated population of healthy adults who had never been positively diagnosed with or vaccinated against SARS-CoV-2, we found that 35.5% (178 out of 501) were positive for SARS-CoV-2-specific IgG and 52.5% (263 out of 501) were positive for SARS-CoV-2-specific IgA; 21.6% of the investigated population developed virus-specific IgG or IgA while being asymptomatic. Anti-RBD IgG, which represents virus-neutralizing potential, was found in 25.6% of individuals (128 out of 501). These patients, though positive for anti-SARS-CoV-2 antibodies, cannot be identified in the public health system as convalescents due to undiagnosed infections, and they are considered unaffected by SARS-CoV-2. Their contribution to population immunity against COVID-19 should however be considered in predictions and modeling of the COVID-19 pandemic. Of note, the majority of the investigated population still lacked anti-RBD IgG protection (74.4%); thus the positive fraction is not sufficient for effective population immunity, and vaccination against COVID-19 is still of the most importance for controlling the pandemic.

  🖺 Full Text HTML: Hidden fraction of Polish population immune to SARS-CoV-2 in May 2021
• Occupational risks of COVID-19 in NHS workers in England -

  Abstract Objective To quantify occupational risks of Covid-19 among healthcare staff during the first wave of the pandemic in England Methods Using pseudonymised data on 902,813 individuals continuously employed by 191 National Health Service trusts during 1.1.19 to 31.7.20, we explored demographic and occupational risk factors for sickness absence ascribed to Covid-19 during 9.3.20 to 31.7.20 (n = 92,880). We estimated odds ratios (ORs) by multivariable logistic regression. Results With adjustment for employing trust, demographic characteristics, and previous frequency of sickness absence, risk relative to administrative/clerical occupations was highest in additional clinical services (including care assistants) (OR 2.31 [2.25-2.37]), registered nursing and midwifery professionals (OR 2.28 [2.23-2.34]) and allied health professionals (OR 1.94 [1.88-2.01]), and intermediate in doctors and dentists (OR 1.55 [1.50-1.61]). Differences in risk were higher after the employing trust had started to care for documented Covid-19 patients, and were reduced, but not eliminated, following additional adjustment for exposure to infected patients or materials, assessed by a job-exposure matrix. For prolonged Covid-19 sickness absence (episodes lasting >14 days), the variation in risk by staff group was somewhat greater. Conclusions After allowance for possible bias and confounding by non-occupational exposures, we estimated that relative risks for Covid-19 among most patient-facing occupations were between 1.5 and 2.5. The highest risks were in those working in additional clinical services, nursing and midwifery and in allied health professions. Better protective measures for these staff groups should be a priority. Covid-19 may meet criteria for compensation as an occupational disease in some healthcare occupations.

  🖺 Full Text HTML: Occupational risks of COVID-19 in NHS workers in England
• Effectiveness of Tocilizumab, Sarilumab, and Anakinra for critically ill patients with COVID-19 The REMAP-CAP COVID-19 Immune Modulation Therapy Domain Randomized Clinical Trial -

  BACKGROUND: The interleukin-6 receptor antagonist tocilizumab improves outcomes in critically ill patients with coronavirus disease 2019 (COVID-19). However, the effectiveness of other immune modulating agents is unclear. METHODS: We evaluated four immunomodulatory agents in an ongoing international, multifactorial, adaptive platform trial. Adult participants with COVID-19 were randomized to receive tocilizumab, sarilumab, anakinra, or standard care (control). In addition, a small group (n=21) of participants were randomized to interferon-beta1a. The primary outcome was an ordinal scale combining in-hospital mortality (assigned -1) and days free of organ support to day 21. The trial used a Bayesian statistical model with pre-defined triggers for superiority, equivalence or futility. RESULTS: Statistical triggers for equivalence between tocilizumab and sarilumab; and for inferiority of anakinra to the other active interventions were met at a planned adaptive analysis. Of the 2274 critically ill participants enrolled, 972 were assigned to tocilizumab, 485 to sarilumab, 378 to anakinra and 418 to control. Median organ support-free days were 7 (interquartile range [IQR] -1, 16), 9 (IQR -1, 17), 0 (IQR -1, 15) and 0 (IQR -1, 15) for tocilizumab, sarilumab, anakinra and control, respectively. Median adjusted odds ratios were 1.46 (95%CrI 1.13, 1.87), 1.50 (95%CrI 1.13, 2.00), and 0.99 (95%CrI 0.74, 1.35) for tocilizumab, sarilumab and anakinra, yielding 99.8%, 99.8% and 46.6% posterior probabilities of superiority, respectively, compared to control. Median adjusted odds ratios for hospital survival were 1.42 (95%CrI 1.05,1.93), 1.51 (95%CrI 1.06, 2.20) and 0.97 (95%CrI 0.66, 1.40) for tocilizumab, sarilumab and anakinra respectively, compared to control, yielding 98.8%, 98.8% and 43.6% posterior probabilities of superiority, respectively, compared to control. All treatments appeared safe. CONCLUSIONS: In patients with severe COVID-19 receiving organ support, tocilizumab and sarilumab are similarly effective at improving survival and reducing duration of organ support. Anakinra is not effective in this population.

  🖺 Full Text HTML: Effectiveness of Tocilizumab, Sarilumab, and Anakinra for critically ill patients with COVID-19 The REMAP-CAP COVID-19 Immune Modulation Therapy Domain Randomized Clinical Trial
• Excess deaths in Spain during the first year of the COVID-19 pandemic outbreak from age/sex-adjusted death rates -

  The Eurostat records of weekly deaths disaggregated by AGEGRP5 (five-year bin age groups) and sex group in Spain have been analyzed to build age/sex-specific weekly death rates and the age/sex-adjusted weekly death rate and to infer the predicted death rate, the excess death rate and the excess deaths during the first year (52-week) of the pandemic. Adjusted rate were computed extending the last available population structure back in time to assess the death rates that should have been observed in the past with the present population structure. Age/sex-adjusted, 52-week death rate had not been as high as the observed rate 10.67 per 1k population in the past 13 years. Poisson regression predicted death rate of 8.81 deaths per 1k population which made an excess death rate of 1.86 deaths per 1k population (Pscore=21.2% and zscore=11.9) with an unbiased standard deviation of the residuals equal to 0.156 deaths per 1k population. This translates into 88242 excess deaths (46695 males and 41532 females) with an unbiased standard deviation of the residuals equal to 7396 deaths. COVID–19 deaths (73516 deaths) accounts for 83% of the total excess. Taking into account the 9772 COVID-19 suspected deaths that occurred in nursing homes and care facilities during the spring of 2020 it is only 4950 (5.6 % of excess deaths) that remains unattributed. The infection rate during the first year of the pandemic is estimated in 17 % of population after comparing the ENE-COVID seroprevalence, the excess deaths at the end of the spring 2020 and the excess deaths at the end of the first year of the pandemic.

  🖺 Full Text HTML: Excess deaths in Spain during the first year of the COVID-19 pandemic outbreak from age/sex-adjusted death rates
• Scientific literacy linked to attitudes toward COVID-19 vaccinations: A pre-registered study -
  The ongoing COVID-19 pandemic, which began in early 2020, is a global public health crisis. To prevent the spread of COVID-19, it is necessary to promote vaccine administration and preventive behaviors (e.g., mask, handwashing, social distancing). However, some people have negative attitudes toward vaccine administration and preventive behaviors. Based on the information-deficit model, the present study investigated how scientific literacy and perceived understanding of COVID-19 are associated with attitudes toward COVID-19 vaccinations and preventive behaviors. The findings demonstrated that both scientific literacy and perceived understanding of COVID-19 vaccines were positively associated with attitudes toward COVID-19 vaccines. Additionally, perceived understanding of COVID-19 preventive behaviors (but not scientific literacy) was positively associated with attitudes toward/practice of COVID-19 preventive behaviors. Collectively, our findings revealed the role of cognitive factors in preventing the global public health crisis and demonstrated the roles of objective and subjective knowledge on attitudes toward COVID-19 vaccinations and preventive behaviors.
  🖺 Full Text HTML: Scientific literacy linked to attitudes toward COVID-19 vaccinations: A pre-registered study
• Hypothetical model of COVID-19: origin,spread,binding,infection,variant,treatment and prevention(Version15） -
  2019 Coronavirus Hypothesis Model, no experiments have been conducted yet, please do not apply this theory before experimental verification. 2019 Coronavirus originates from bats or other animals. In bats, this virus is a cooling factor. Due to the high temperature of bats, this cooling factor cools bats and belongs to normal life activity, it will not produce immune activation, and thus will not produce infections in the bat body. Bat parents spray the virus into the cub’s respiratory system to inherit the virus. When this cooling factor enters the human body, the virus starts to cool the human cell, the chill happens. The human immune system starts a fever to fight the cooling. This explains why COVID-19 has cold symptoms. The higher the body temperature of the bat, the more the virus replicates, the stronger the binding power and the stronger the jetting power,therefore, the fever of the human body promotes the aggravation of the disease. When a large number of people are infected and the environment temperature is high, the virus will mutate, and the cooling capacity, binding power and jetting power will increase, and the epidemic will worsen. When the body temperature of the bat is very low, the virus loses its binding power and is excreted from the body, refrigerant can be inhaled in the human body to expel the virus. Bats use high temperature to eliminate excess cooling factors to prevent the temperature from being too low, put the human body in a higher temperature environment, the heat is transmitted to the body, and the low temperature factor of the 2019 Coronavirus can be overcome.The measured temperature of the 2019 Coronavirus will be relatively lower, which can verify this hypothesis.
  🖺 Full Text HTML: Hypothetical model of COVID-19: origin,spread,binding,infection,variant,treatment and prevention(Version15）
• Structure, activity and inhibition of human TMPRSS2, a protease implicated in SARS-CoV-2 activation -
  Transmembrane protease, serine 2 (TMPRSS2) has been identified as key host cell factor for viral entry and pathogenesis of SARS-coronavirus-2 (SARS-CoV-2). Specifically, TMPRSS2 proteolytically processes the SARS-CoV-2 Spike (S) Protein, enabling virus-host membrane fusion and infection of the lungs. We present here an efficient recombinant production strategy for enzymatically active TMPRSS2 ectodomain enabling enzymatic characterization, and the 1.95 A X-ray crystal structure. To stabilize the enzyme for co-crystallization, we pre-treated TMPRSS2 with the synthetic protease inhibitor nafamosat to form a stable but slowly reversible (15 hour half-life) phenylguanidino acyl-enzyme complex. Our study provides a structural basis for the potent but non-specific inhibition by nafamostat and identifies distinguishing features of the TMPRSS2 substrate binding pocket that will guide future generations of inhibitors to improve selectivity. TMPRSS2 cleaved recombinant SARS-CoV-2 S protein ectodomain at the canonical S1/S2 cleavage site and at least two additional minor sites previously uncharacterized. We established enzymatic activity and inhibition assays that enabled ranking of clinical protease inhibitors with half-maximal inhibitory concentrations ranging from 1.7 nM to 120 uM and determination of inhibitor mechanisms of action. These results provide a body of data and reagents to support future drug development efforts to selectively inhibit TMPRSS2 and other type 2 transmembrane serine proteases involved in viral glycoprotein processing, in order to combat current and future viral threats.
  🖺 Full Text HTML: Structure, activity and inhibition of human TMPRSS2, a protease implicated in SARS-CoV-2 activation
• Lipid and nucleocapsid N-protein accumulation in COVID-19 patient lung and infected cells -
  The trafficking of coronaviruses in lung of COVID-19 patients is not well understood and virus particles are difficult to find. Here we have visualized virus particles in SARS-CoV-2 infected cells by focusing on viral protein detection, in combination with ultrastructure. We studied how the virus is altering the cell morphology and determined that in Vero cells, lipid filled compartments contained various viral proteins. In these cells, also membrane enclosed multi-virus bodies were visible that contain a different set of viral proteins. We demonstrated that lipid filled compartments are novel viral induced compartments, as no known cellular marker such as lipid droplet or lysosomal marker was present. Using this knowledge, we then studied lung tissue from patients with a fatal SARS-Cov-2 infection, processed in a similar manner. Again we detected lipid filled compartments with viral proteins nsp4 and the stable nucleocapsid N-protein. The presence of these lipid filled compartments with viral proteins induced by SARS-CoV-2 infections, could be why the immune response of the COVID-19 patients is so strong, resulting in a fatal infection, and should be considered for new therapeutic strategies.
  🖺 Full Text HTML: Lipid and nucleocapsid N-protein accumulation in COVID-19 patient lung and infected cells
• SARS-CoV-2-Triggered Mast Cell Rapid Degranulation Induces Alveolar Epithelial Inflammation and Lung Injury -
  SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity. Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments. Mast cells (MCs) are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations. Here we showed that SARS-CoV-2-triggeed MC degranulation initiated alveolar epithelial inflammation and lung injury. SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques, and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells; MC degranulation alterred various signaling pathways in alveolar epithelial cells, particularly, led to the production of pro-inflammatory factors and consequential disruption of tight junctions. Importantly, the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury. These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation, and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.
  🖺 Full Text HTML: SARS-CoV-2-Triggered Mast Cell Rapid Degranulation Induces Alveolar Epithelial Inflammation and Lung Injury
• Optimal Selection of COVID-19 Vaccination Sites at the Municipal Level -

  In this work, we present an approach to determine the optimal location of coronavirus disease (COVID-19) vaccination sites at the municipal level. We assume that each municipality or town is subdivided into smaller administrative units, which we refer to as villages or barangays. The proposed method solves a minimization problem arising from a facility location problem, which is formulated based on the proximity of the vaccination sites to the villages, number of COVID-19 cases, and population densities of the villages. We present a numerical scheme to solve the optimization problem and give a detailed description of the algorithm, which is coded in Python. To make the results reproducible, the codes used in this study are uploaded to a public repository, which also contains complete instructions on how to use them. As an illustration, we apply our method in determining the optimal location of vaccination sites in San Juan, a town in the province of Batangas, in the Philippines. We hope that this study may guide the local government units in coming up with strategic plans for the COVID-19 vaccine rollout.

  🖺 Full Text HTML: Optimal Selection of COVID-19 Vaccination Sites at the Municipal Level
• Delay of molecular SARS-CoV-2 testing and turnaround time in Mexico and Colombia -

  Objective: To quantify the delay in SARS-CoV-2 real time polymerase chain reaction (RT-PCR) testing and test result reporting in Mexico and Colombia, and to assess the relation between margination status and these delays. Methods: We quantified time in days from symptom onset until testing (latency one) and delay in test results report (latency two) using freely available country-wide open data from Mexico and Colombia. Directed acyclic graphs were built to determine which associations were appropriate to assess. Stratification by margination status, state and hospitalization status was used to determine corresponding associations. Results: In almost all the study period latency two was longer than latency one. Median latency one was 3 (IQR 0-6) days and latency two 7 (IQR 4-11) days in Colombia, while in Mexico they were 3 (IQR 1-5) days and 4 (IQR 3-6) days. In Colombia, worse margination status prolonged latency two. In Mexico, a lower number and percentage of point-of-care (POC) tests in areas with worse margination. Conclusion: POC tests must be used as a widespread means to reduce latency two, and until then should be prioritized in areas with longer latency two. An unequal distribution of this resource should be avoided.

  🖺 Full Text HTML: Delay of molecular SARS-CoV-2 testing and turnaround time in Mexico and Colombia
• The impact of legislation on Covid-19 mortality in a Brazilian federative unit was mediated by social isolation. -

  This study aimed to estimate the effect of restrictive laws on actual social isolation and COVID-19 mortality. Moreover, we evaluated how community adherence, measured with an index of social isolation, would mediate the lockdown effect on COVID-19 mortality. Methods: This ecological study assessed the legislations published until June 30, 2020, in the Brazilian state of Ceara. We performed a systematic review and classification of restrictive norms and estimated their immediate effect on social isolation, measured by an index based on mobile data, and the subsequent impact on COVID-19 mortality (three weeks later). A mediation analysis was performed to estimate the effect of rigid lockdown on mortality that was explained for effective social isolation. Results: The social isolation index showed an increase of 11.9% (95% CI: 2.9% - 21%) during the days in which a rigid isolation norm (lockdown) was implemented. Moreover, this rigid lockdown was associated with a reduction of 26% (95% CI: 21% - 31%) in the three-week-delayed mortality. We also calculated that the rigid lockdown had the indirect effect, i.e., mediated by adherence to social isolation, of reducing COVID-19 mortality by 38.24% (95% CI: 21.64% to 56.07%). Therefore, the preventive effect of this norm was fully explained by the actual population adherence, reflected in the social isolation index. On the other hand, mandatory mask use was associated with 11% reduction in COVID-19 mortality (95% CI: 8% - 13%). Conclusions: We estimated the effect of quarantine regulations on social isolation and evidenced that a rigid lockdown law led to a reduction of COVID-19 mortality in one state of Brazil. In addition, the mandatory masks norm was an additional determinant of the reduction of this outcome.

  🖺 Full Text HTML: The impact of legislation on Covid-19 mortality in a Brazilian federative unit was mediated by social isolation.
• OVARIAN GRANULOSA CELLS FROM WOMEN WITH PCOS EXPRESS LOW LEVELS OF SARS-COV-2 RECEPTORS AND CO-FACTORS -

  Purpose: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is global pandemic with more than 3 million deaths so far. Female reproductive tract organs express coronavirus-associated receptors and factors (SCARFs); suggesting they may be susceptible to SARS-CoV-2 infection however the susceptibility of ovary/follicle/oocyte to the same is still elusive. Co-morbidities like obesity, type-2 diabetes mellitus, cardiovascular disease etc. increase the risk of SARS-CoV-2 infection. These features are common in women with polycystic ovary syndrome (PCOS), warranting further scope to study SCARFs expression in ovary of these women. Materials and methods: SCARFs expression in ovary and ovarian tissues of women with PCOS and healthy women was explored by analyzing publically available microarray datasets. Transcript expression of SCARFs were investigated in mural and cumulus granulosa cells (MGCs and CGCs) from control and PCOS women undergoing in vitro fertilization (IVF). Results: Microarray data revealed that ovary expresses all genes necessary for SARS-CoV-2 infection. PCOS women mostly showed down-regulated/unchanged levels of SCARFs. MGCs and CGCs from PCOS women showed lower expression of receptors ACE2, BSG and DPP4 and protease CTSB than in controls. MGCs showed lower expression of protease CTSL in PCOS than in controls. Expression of TMPRSS2 was not detected in both cell types. Conclusions: Human ovarian follicle may be susceptible to SARS-CoV-2 infection. Lower expression of SCARFs in PCOS indicate that the risk of SARS-CoV-2 infection to the ovary may be lesser in these women than controls. This knowledge may help in safe practices at IVF settings in the current pandemic. Keywords: SARS-CoV-2, COVID-19, Ovarian granulosa cells, Oocyte, PCOS, IVF

  🖺 Full Text HTML: OVARIAN GRANULOSA CELLS FROM WOMEN WITH PCOS EXPRESS LOW LEVELS OF SARS-COV-2 RECEPTORS AND CO-FACTORS
• Allicin inhibits SARS-CoV-2 replication and abrogates the antiviral host response in the Calu-3 proteome -
  The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic is a major health burden. Volatile garlic organosulfur compounds, such as the thiol-reactive allicin (diallyl thiosulfinate) exert strong antimicrobial activity against various respiratory pathogens. Here, we investigated the antiviral activity of allicin against SARS-CoV-2 in infected Vero E6 and Calu-3 lung cells. Calu-3 cells showed greater allicin tolerance due >4-fold increased GSH levels compared to Vero E6. However, biocompatible allicin doses efficiently inhibited viral replication in both cell lines. Proteome analyses of SARS-CoV-2 infected Calu-3 cells revealed a strong induction of the antiviral interferon-stimulated gene (ISG) signature (e.g. cGAS, Mx1, IFIT, IFIH, IFI16, IFI44,OAS and ISG15), pathways of vesicular transport, tight junctions (KIF5A/B/C, OSBPL2, CLTC1, ARHGAP17) and ubiquitin modification (UBE2L3/5), as well as reprogramming of host metabolism, transcription and translation. Allicin abrogated the ISG host response and reverted the host cellular pathways to levels of uninfected Calu-3 cells, confirming the antiviral and immunomodulatory activity of allicin in the host proteome. Thus, biocompatible doses of allicin could be promising for protection of lung cells against SARS-CoV-2.
  🖺 Full Text HTML: Allicin inhibits SARS-CoV-2 replication and abrogates the antiviral host response in the Calu-3 proteome

From Clinical Trials

• MP1032 Treatment in Patients With Moderate to Severe COVID-19 - Condition:   COVID-19
  Interventions:   Drug: MP1032;   Drug: Placebo
  Sponsors:   MetrioPharm AG;   Syneos Health, LLC
  Not yet recruiting

• Efficacy and Safety of XAV-19 for the Treatment of Moderate-to-severe COVID-19 - Condition:   COVID-19
  Interventions:   Drug: XAV-19;   Drug: Placebo
  Sponsor:   Xenothera SAS
  Recruiting

• In Situ Thrombolysis With tPA and Inflow Perfusion Analysis in Patient With Severe Covid-19 Infection - Condition:   COVID-19
  Intervention:   Drug: tPA
  Sponsor:   Grupo Mexicano para el Estudio de la Medicina Intensiva
  Completed

• Clinical Trial With N-acetylcysteine and Bromhexine for COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Vitamin C;   Drug: N-acetylcysteine (NAC);   Drug: NAC + Bromhexine (BMX)
  Sponsors:   Universidade Federal do Ceara;   Paulista School of Medicine-EPM, UNIFESP;   Health Surveillance Secretariat - SVS;   Central Laboratory of Public Health of Ceara - LACEN-CE;   Leonardo da Vinci Hospital - HLV;   São José Hospital for Infectious Diseases - HSJ;   Ceará Health Secretariat - SESA;   Municipal Health Secretary - SMS-Fortaleza
  Not yet recruiting

• Safety and Immunogenicity of LNP-nCOV saRNA-02 Vaccine Against SARS-CoV-2, the Causative Agent of COVID-19 - Condition:   COVID-19
  Intervention:   Drug: LNP-nCOV saRNA-02 Vaccine
  Sponsor:   MRC/UVRI and LSHTM Uganda Research Unit
  Not yet recruiting

• Study to Evaluate the Safety and Concentrations of Monoclonal Antibody Against Virus That Causes COVID-19 Disease. - Condition:   COVID-19 Virus Disease
  Interventions:   Biological: MAD0004J08;   Other: Placebo
  Sponsors:   Toscana Life Sciences Sviluppo s.r.l.;   Cross Research S.A.
  Active, not recruiting

• Dapsone Coronavirus SARS-CoV-2 Trial (DAP-CORONA) COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Dapsone 85 mg PO BID;   Drug: Placebo 85 mg PO BID
  Sponsors:   McGill University Health Centre/Research Institute of the McGill University Health Centre;   Pulmonem Inc.
  Not yet recruiting

• Infliximab in the Treatment of Patients With Severe COVID-19 Disease - Condition:   COVID-19
  Interventions:   Drug: Infliximab;   Other: Standard of Care
  Sponsors:   Jena University Hospital;   German Federal Ministry of Education and Research;   Celltrion
  Not yet recruiting

• Long-term Follow-up to the Phase 1 Study of Adjuvanted SARS-CoV-2 (SCB 2019) Vaccine for COVID-19. - Condition:   COVID-19
  Intervention:   Biological: SCB-2019
  Sponsor:   Clover Biopharmaceuticals AUS Pty Ltd
  Recruiting

• IRAK 4 Inhibitor (PF-06650833) in Hospitalized Patients With COVID-19 Pneumonia and Exuberant Inflammation. - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: PF-06650833;   Drug: Matching Placebo
  Sponsors:   Giovanni Franchin, M.D, Ph.D;   Pfizer
  Recruiting

• Tolerability,Safety of JS016 in SARS-CoV-2 (COVID-19) - Conditions:   COVID-19;   SARS-CoV-2
  Intervention:   Drug: Combination Product: JS016 (anti-SARS-CoV-2 monoclonal antibody)
  Sponsor:   Peking Union Medical College Hospital
  Recruiting

• Cerebral Autoregulation and COVID-19 - Conditions:   COVID-19 Acute Respiratory Distress Syndrome;   COVID-19 Pneumonia
  Intervention:   Other: NIRS (Near-Infrared Spectroscopy)
  Sponsor:   University of Athens
  Not yet recruiting

• Cognitive and Psychological Disorders After Severe COVID-19 Infection - Condition:   COVID 19
  Interventions:   Diagnostic Test: Cognitive assessment;   Diagnostic Test: Imaging;   Diagnostic Test: Routine care;   Other: Psychiatric evaluation
  Sponsors:   Central Hospital, Nancy, France;   Centre Hospitalier Universitaire de Besancon;   University Hospital, Strasbourg, France;   Centre Hospitalier Régional Metz-Thionville;   Centre hospitalier Epinal;   Hopitaux Civils de Colmar
  Not yet recruiting

• Study of Codivir in Patients With COVID-19 - Condition:   Covid19
  Interventions:   Drug: Covidir injections;   Diagnostic Test: One Step Test;   Diagnostic Test: IgM and IgG dosage;   Diagnostic Test: RT-PCR SARS-CoV-2;   Diagnostic Test: Screening blood test;   Diagnostic Test: ECG;   Diagnostic Test: Medical evaluation;   Diagnostic Test: NEWS-2 score;   Diagnostic Test: WHO score
  Sponsors:   Code Pharma;   Zion Medical
  Active, not recruiting

• Study to Evaluate the Safety, Immunogenicity, and Efficacy of Nanocovax Vaccine Against COVID-19 - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Interventions:   Biological: Nanocovax;   Biological: Placebo
  Sponsor:   Nanogen Pharmaceutical Biotechnology Joint Stock Company
  Recruiting

From PubMed

• Rationale, study design and implementation of the LUCINDA Trial: Leuprolide plus cholinesterase inhibition to reduce neurologic decline in Alzheimer’s - The LUCINDA Trial (Leuprolide plus Cholinesterase Inhibition to reduce Neurologic Decline in Alzheimer’s) is a 52 week, randomized, placebo-controlled trial of leuprolide acetate (Eligard) in women with Alzheimer’s disease (AD). Leuprolide acetate is a gonadotropin analogue commonly used for hormone-sensitive conditions such as prostate cancer and endometriosis. This repurposed drug demonstrated efficacy in a previous Phase II clinical trial in those women with AD who also received a stable dose…

• Rapid, reliable, and reproducible cell fusion assay to quantify SARS-Cov-2 spike interaction with hACE2 - COVID-19 is a global crisis of unimagined dimensions. Currently, Remedesivir is only fully licensed FDA therapeutic. A major target of the vaccine effort is the SARS-CoV-2 spike-hACE2 interaction, and assessment of efficacy relies on time consuming neutralization assay. Here, we developed a cell fusion assay based upon spike-hACE2 interaction. The system was tested by transient co-transfection of 293T cells, which demonstrated good correlation with standard spike pseudotyping for inhibition by…

• SARS-CoV-2 viral proteins NSP1 and NSP13 inhibit interferon activation through distinct mechanisms - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating global pandemic, infecting over 43 million people and claiming over 1 million lives, with these numbers increasing daily. Therefore, there is urgent need to understand the molecular mechanisms governing SARS-CoV-2 pathogenesis, immune evasion, and disease progression. Here, we show that SARS-CoV-2 can block IRF3 and NF-κB activation early during virus infection. We also identify that the SARS-CoV-2 viral…

• Mechanism of inhibition of SARS-CoV-2 M(pro) by N3 peptidyl Michael acceptor explained by QM/MM simulations and design of new derivatives with tunable chemical reactivity - The SARS-CoV-2 main protease (M^(pro)) is essential for replication of the virus responsible for the COVID-19 pandemic, and one of the main targets for drug design. Here, we simulate the inhibition process of SARS-CoV-2 M^(pro) with a known Michael acceptor (peptidyl) inhibitor, N3. The free energy landscape for the mechanism of the formation of the covalent enzyme-inhibitor product is computed with QM/MM molecular dynamics methods. The simulations show a two-step mechanism, and give structures…

• Inhibitors of thiol-mediated uptake - Ellman’s reagent has caused substantial confusion and concern as a probe for thiol-mediated uptake because it is the only established inhibitor available but works neither efficiently nor reliably. Here we use fluorescent cyclic oligochalcogenides that enter cells by thiol-mediated uptake to systematically screen for more potent inhibitors, including epidithiodiketopiperazines, benzopolysulfanes, disulfide-bridged γ-turned peptides, heteroaromatic sulfones and cyclic thiosulfonates,…

• A microscopic description of SARS-CoV-2 main protease inhibition with Michael acceptors. Strategies for improving inhibitor design - The irreversible inhibition of the main protease of SARS-CoV-2 by a Michael acceptor known as N3 has been investigated using multiscale methods. The noncovalent enzyme-inhibitor complex was simulated using classical molecular dynamics techniques and the pose of the inhibitor in the active site was compared to that of the natural substrate, a peptide containing the Gln-Ser scissile bond. The formation of the covalent enzyme-inhibitor complex was then simulated using hybrid QM/MM free energy…

• Hyper-Enriched Anti-RSV Immunoglobulins Nasally Administered: A Promising Approach for Respiratory Syncytial Virus Prophylaxis - Respiratory syncytial virus (RSV) is a public health concern that causes acute lower respiratory tract infection. So far, no vaccine candidate under development has reached the market and the only licensed product to prevent RSV infection in at-risk infants and young children is a monoclonal antibody (Synagis^(®)). Polyclonal human anti-RSV hyper-immune immunoglobulins (Igs) have also been used but were superseded by Synagis^(®) owing to their low titer and large infused volume. Here we report a…

• Therapeutic Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 - Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients….

• Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19 - CONCLUSION: Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of patients with mild COVID-19 with rapid viral clearance and shortening the anosmia duration.

• Structure-guided design of a perampanel-derived pharmacophore targeting the SARS-CoV-2 main protease - There is a clinical need for direct-acting antivirals targeting SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, to complement current therapeutic strategies. The main protease (M^(pro)) is an attractive target for antiviral therapy. However, the vast majority of protease inhibitors described thus far are peptidomimetic and bind to the active-site cysteine via a covalent adduct, which is generally pharmacokinetically unfavorable. We have reported the optimization of an existing…

• It - ObjectiveMindStep™ is an Australian low-intensity cognitive behaviour therapy (LICBT) program for individuals with mild-to-moderate symptoms of anxiety and depression. UK-produced LICBT guided self-help (GSH) materials were originally used in the MindStep™ program. In 2017, Australian LICBT GSH materials were developed to better suit Australian users. This study explored whether the Australian-produced materials continued to achieve the benchmark recovery rates established in the UK and…

• Structural basis of covalent inhibitory mechanism of TMPRSS2-related serine proteases by camostat - SARS-CoV-2 is the viral pathogen causing the COVID19 global pandemic. No effective treatment for COVID-19 has been established yet. TMPRSS2 is essential for viral spread and pathogenicity by facilitating the entry of SARS-CoV-2 onto host cells. The protease inhibitor camostat, an anticoagulant used in the clinic, has potential anti-inflammatory and anti-viral activities against COVID-19. However, the potential mechanisms of viral resistance and antiviral activity of camostat are unclear. Herein,…

• SARS-CoV-2 spike protein induces paracrine senescence and leukocyte adhesionin endothelial cells - Increased mortality in COVID-19 often associates with microvascular complications. We have recently shown that SARS-CoV-2 spike protein promotes an inflammatory cytokine IL-6/IL-6R induced trans-signaling response and alarmin secretion. Virus infected or spike transfected human epithelial cells exhibited an increase in senescence state with the release of senescence associated secretory proteins (SASP) related inflammatory molecules. Introduction of BRD4 inhibitor AZD5153 to senescent epithelial…

• Structure-based virtual screening of bioactive compounds from Indonesian medical plants against severe acute respiratory syndrome coronavirus-2 - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a virus that causes the infectious disease coronavirus disease-2019. Currently, there is no effective drug for the prevention and treatment of this virus. This study aimed to identify secondary metabolites that potentially inhibit the key proteins of SARS-CoV-2. This was an in silico molecular docking study of several secondary metabolites of Indonesian herbal plant compounds and other metabolites with antiviral testing history….

• TRPV2-spike protein interaction mediates the entry of SARS-CoV-2 into macrophages in febrile conditions - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel strain of highly contagious coronaviruses that infects humans. Prolonged fever, particularly that above 39.5 °C, is associated with SARS-CoV-2 infection. However, little is known about the pathological effects of fever caused by SARS-CoV-2. Methods: Primary bovine alveolar macrophages (PBAMs), RAW264.7 mouse macrophages, and THP-1 human cells were transfected with plasmids carrying the genes encoding the SARS-CoV-2 spike (S)…

From Patent Search

• SARS-CoV-2 anti-viral therapeutic - - link

• 폐마스크 밀봉 회수기 - 본 발명은 마스크 착용 후 버려지는 일회용 폐마스크를 비닐봉지에 넣은 후 밀봉하여 배출함으로써, 2차 감염을 예방하고 일반 생활폐기물과 선별 분리 배출하여 환경오염을 방지하는 데 그 목적이 있다. - link

• COST EFFECTIVE PORTABLE OXYGEN CONCENTRATOR FOR COVID-19 - - link

• METHOD OF IDENTIFYING SEVERE ACUTE RESPIRATORY SYNDROME CORONA VIRUS 2 (SARS-COV-2) RIBONUCLEIC ACID (RNA) - - link

• Erweiterbare Desinfektionsvorrichtung -

  Erweiterbare Desinfektionsvorrichtung, umfassend: einen Hauptkörper, der eine umgekehrt U-förmige Basisplatte aufweist, wobei die umgekehrt U-förmige Basisplatte mit einer Öffnung versehen ist und jeweils eine Seitenplatte sich von zwei Seiten der umgekehrt U-förmigen Basisplatte nach außen erstreckt; und mindestens eine Desinfektionslampe, die in den auf zwei Seiten des Hauptkörpers befindlichen Seitenplatten angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst.

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• Einfache Sterilisationsvorrichtung -

  Einfache Sterilisationsvorrichtung, mit einem Hauptkörper (11), der in Längsrichtung einen ersten Plattenabschnitt (111) und in Querrichtung einen zweiten Plattenabschnitt (112) aufweist, wobei der erste Plattenabschnitt (111) und der zweite Plattenabschnitt (112) L-förmig miteinander verbunden sind; und einer Sterilisationslampe (12), die an dem Hauptkörper (11) angeordnet ist und eine Lichtemissionseinheit (121), eine Sensoreinheit (122), eine Steuereinheit (123) und eine Stromeinheit (124) aufweist.

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• Klemmarme aufweisende Desinfektionsvorrichtung -

  Klemmarme aufweisende Desinfektionsvorrichtung, umfassend: einen Hauptkörper; eine Desinfektionslampe, die im Hauptkörper angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst; einen Klemmabschnitt, der auf einer Seite des Hauptkörpers angeordnet ist, wobei der Klemmabschnitt zwei gegenüberliegende Greifbacken umfasst, wobei mindestens eine der beiden Greifbacken mit einer Schwenkachse versehen ist, wobei ein Klemmraum durch passgenaues Schließen der beiden Greifbacken entsteht und die beiden Greifbacken jeweils mit einem Durchgangsloch versehen sind; einen Befestigungsabschnitt, der durch die Durchgangslöcher der beiden Greifbacken hindurchgeführt ist;und ein Schild, das auf einer Seite des Klemmabschnitts angeordnet und mit einem Aufnahmeloch versehen ist.

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• Aufhängbare Sterilisationsvorrichtung -

  Aufhängbare Sterilisationsvorrichtung, mit einem Hauptkörper (11); einer Sterilisationslampe (12), die an dem Hauptkörper (11) angeordnet ist und eine Lichtemissionseinheit (121), eine Sensoreinheit (122), eine Steuereinheit (123) und eine Stromeinheit (124) aufweist; einem Klemmabschnitt (13), der an einer Seite des Hautpkörpers (11) angeordnet ist und zwei gegenüberliegend angeordnete Klemmbacken (131) aufweist, wobei mindestens eine der beiden Klemmbacken (131) mit einem Achsbolzen (132) versehen ist, wobei die beiden Klemmbacken (131) beim Schließen einen Klemmraum (134) bilden, und wobei die beiden Klemmbacken (131) jeweils mit einem Durchgangsloch (135) versehen sind; und einem Befestigungselement (14), das durch die Durchgangslöcher (135) der beiden Klemmbacken (131) hindurchgeführt wird.

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• Sterilisationsvorrichtung zur Verbesserung der Desinfektionswirkung -

  Sterilisationsvorrichtung zur Verbesserung der Desinfektionswirkung, umfassend: einen Hauptkörper, der eine erste Oberfläche, eine von der ersten Oberfläche abgewandte zweite Oberfläche und ein Aufnahmeloch aufweist, wobei die zwei Seiten des Hauptkörpers jeweils mit einem Durchgangsloch versehen sind, wobei die Durchgangslöcher mit dem Aufnahmeloch durchgängig verbunden sind; eine Desinfektionslampe, die auf der zweiten Oberfläche des Hauptkörpers angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst; und ein Befestigungsteil, das durch die Durchgangslöcher und das Aufnahmeloch des Hauptkörpers hindurchgeführt ist.

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• IMPROVEMENTS RELATED TO PARTICLE, INCLUDING SARS-CoV-2, DETECTION AND METHODS THEREFOR - - link